Multiple courses of penicillins may modestly increase the risk of developing colorectal cancer (CRC), according to researchers who used a UK database to match 20,990 people with the malignancy with 82,054 controls.

Neither antivirals nor antifungals influenced CRC risk during a median follow-up of 6.5 years. Initial antibiotic use more than one year before the index date increased CRC risk among patients taking nitroimidazoles (9 per cent), penicillins (6 per cent), cephalosporins (5 per cent) and trimethoprim plus sulfamethoxazole (5 per cent).

Macrolides and tetracyclines did not seem to increase CRC risk. Highest risk The highest risk emerged in people who received their first antibiotic prescription during the six months before CRC diagnosis. No statistically significant association emerged between CRC and first antibiotic use beyond five years, except for penicillin. Patients first exposed to penicillins more than 10 years before diagnosis were 11 per cent more likely to develop CRC than controls.

Risk rose with the number of courses, reaching a 20 and 25 per cent increased risk in those who received more than 10 courses of penicillins and cephalosporins respectively. The risk rose by 4 per cent for each additional course of penicillin each year.

The authors suggest that penicillin might alter colonic microbiota – which previous studies suggested predisposes to CRC – contributing to the progression from adenoma to carcinoma.

However, repeated antibiotic exposure might be needed to produce a lasting change in the diversity of colonic bacteria. The difference between antibiotics might reflect their spectrum of action. Penicillins that mainly target gram-positive bacteria might enable growth of Bacteroides species, which previous studies suggested were especially common in CRC patients. (Pharmacoepidem Drug Saf doi: 10.1002/pds. 3765)